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World Journal of Surgical Oncology Apr 2021BLCA is a common cancer worldwide, and it is both aggressive and fatal. Immunotherapy (ICT) has achieved an excellent curative effect in BLCA; however, only some BLCA...
BACKGROUND
BLCA is a common cancer worldwide, and it is both aggressive and fatal. Immunotherapy (ICT) has achieved an excellent curative effect in BLCA; however, only some BLCA patients can benefit from ICT. MT1L is a pseudogene, and a previous study suggested that MT1L can be used as an indicator of prognosis in colorectal cancer. However, the role of MT1L in BLCA has not yet been determined.
METHODS
Data were collected from TCGA, and logistic regression, Kaplan-Meier plotter, and multivariate Cox analysis were performed to demonstrate the correlation between the pseudogene MT1L and the prognosis of BLCA. To identify the association of MT1L with tumor-infiltrating immune cells, TIMER and TISIDB were utilized. Additionally, GSEA was performed to elucidate the potential biological function.
RESULTS
The expression of MT1L was decreased in BLCA. Additionally, MT1L was positively correlated with immune cells, such as Tregs (ρ = 0.708) and MDSCs (ρ = 0.664). We also confirmed that MT1L is related to typical markers of immune cells, such as PD-1 and CTLA-4. In addition, a high MT1L expression level was associated with the advanced T and N and high grade in BLCA. Increased expression of MT1L was significantly associated with shorter OS times of BLCA patients (p < 0.05). Multivariate Cox analysis revealed that MT1L expression could be an independent prognostic factor in BLCA.
CONCLUSION
Collectively, our findings demonstrated that the pseudogene MT1L regulates the immune microenvironment, correlates with poor survival, and is an independent prognostic biomarker in BLCA.
Topics: Colonic Neoplasms; Gene Expression Regulation, Neoplastic; Humans; Prognosis; Pseudogenes; Tumor Microenvironment; Urinary Bladder Neoplasms
PubMed: 33888142
DOI: 10.1186/s12957-021-02231-4 -
Reports of Practical Oncology and... 2023Skin melanoma is one of the deadliest types of skin cancer and develops from melanocytes. The genetic aberrations in protein-coding genes are well characterized, but...
BACKGROUND
Skin melanoma is one of the deadliest types of skin cancer and develops from melanocytes. The genetic aberrations in protein-coding genes are well characterized, but little is known about changes in non-coding RNAs (ncRNAs) such as pseudogenes. Ribosomal protein pseudogenes (RPPs) have been described as the largest group of pseudogenes which are dispersed in the human genome.
MATERIALS AND METHIDS
We looked deeply at the role of one of them, ribosomal protein L23a pseudogene 53 (), and its potential diagnostic use. The expression level of was profiled in melanoma cell lines using real time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and analyzed based on the Cancer Genome Atlas (TCGA) data depending on status and clinicopathological parameters. Cellular phenotype, which was associated with levels, was described based on the REACTOME pathway browser, Gene Set Enrichment Analysis (GSEA) analysis as well as Immune and ESTIMATE Scores.
RESULTS
We indicted changes in level depending on a cell line, and based on analysis of TCGA samples demonstrated significant differences in expression between primary and metastatic melanoma, as well as correlation between and overall survival. No differences depending on status were observed. is associated with several signaling pathways and cellular processes.
CONCLUSIONS
This study showed that patients with higher expression of displayed changed infiltration of lymphocytes, macrophages, and neutrophils compared to groups with lower expression of . pseudogene is differently expressed in melanoma compared with normal tissue and its expression is associated with cellular proliferation. Thus, it may be considered as an indicator of patients' survival and a marker for the immune profile assessment.
PubMed: 37456695
DOI: 10.5603/RPOR.a2023.0030 -
Annual Review of Plant Biology Apr 2020L. is an important yet controversial plant with a long history of recreational, medicinal, industrial, and agricultural use, and together with its sister genus , it... (Meta-Analysis)
Meta-Analysis
L. is an important yet controversial plant with a long history of recreational, medicinal, industrial, and agricultural use, and together with its sister genus , it represents a group of plants with a myriad of academic, agricultural, pharmaceutical, industrial, and social interests. We have performed a meta-analysis of pooled published genomics data, andwe present a comprehensive literature review on the evolutionary history of and , including medicinal and industrial applications. We demonstrate that current genome assemblies are incomplete, with ∼10% missing, 10-25% unmapped, and 45S and 5S ribosomal DNA clusters as well as centromeres/satellite sequences not represented. These assemblies are also ordered at a low resolution, and their consensus quality clouds the accurate annotation of complete, partial, and pseudogenized gene copies. Considering the importance of genomics in the development of any crop, this analysis underlines the need for a coordinated effort to quantify the genetic and biochemical diversity of this species.
Topics: Cannabis; Family; Genomics; Humulus
PubMed: 32155342
DOI: 10.1146/annurev-arplant-081519-040203 -
Cell Cycle (Georgetown, Tex.) Sep 2020Latest studies have shown that deregulated pseudogene transcripts contribute to cancer working as competing endogenous RNAs. Our research group has recently demonstrated...
Latest studies have shown that deregulated pseudogene transcripts contribute to cancer working as competing endogenous RNAs. Our research group has recently demonstrated that the overexpression of two pseudogenes, and , has a critical role in cancer progression. These pseudogenes work sustaining the expression of HMGA1 and other cancer-related genes. We generated a mouse model overexpressing to better study the -pseudogene function in a more physiological context. Here, we show the proliferation rate and the susceptibility to senescence of mouse embryonic fibroblasts obtained from -overexpressing mice to better characterize the HMGA1-pseudogene function. Indeed, our study reports that mouse embryonic fibroblasts (MEFs) derived from mice express higher HMGA1 mRNA and protein levels. Moreover, these cells grow faster and senesce later than wild-type sustaining the oncogenic role of ceRNA crosstalk mediated by .
Topics: Animals; Cell Proliferation; Cells, Cultured; Cellular Senescence; Embryo, Mammalian; Fibroblasts; HMGA1a Protein; Humans; Mice, Transgenic; Pseudogenes; Up-Regulation
PubMed: 32787507
DOI: 10.1080/15384101.2020.1807080 -
Frontiers in Immunology 2019Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population with potent immunosuppressive functions. They play major roles in cancer and many of the... (Review)
Review
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population with potent immunosuppressive functions. They play major roles in cancer and many of the pathologic conditions associated with inflammation. Long non-coding RNAs (lncRNAs) are untranslated functional RNA molecules. The lncRNAs are involved in the control of a wide variety of cellular processes and are dysregulated in different diseases. They can participate in the modulation of immune function and activity of inflammatory cells, including MDSCs. This mini review focuses on the emerging role of lncRNAs in MDSC activity. We summarize how lncRNAs modulate the generation, recruitment, and immunosuppressive functions of MDSCs and the underlying mechanisms.
Topics: Animals; CCAAT-Enhancer-Binding Protein-beta; Cell Lineage; Epigenesis, Genetic; Forecasting; Gene Expression Regulation, Neoplastic; Humans; Immunotherapy; Inflammation; Mice; Myeloid-Derived Suppressor Cells; Neoplasms; Nitric Oxide; Pseudogenes; RNA, Long Noncoding; RNA, Neoplasm; Reactive Oxygen Species; Tumor Escape; Tumor Microenvironment
PubMed: 31404149
DOI: 10.3389/fimmu.2019.01734 -
Scientific Reports Apr 2020We have recently identified and characterized two pseudogenes (HMGA1P6 and HMGA1P7) of the HMGA1 gene, which has a critical role in malignant cell transformation and...
We have recently identified and characterized two pseudogenes (HMGA1P6 and HMGA1P7) of the HMGA1 gene, which has a critical role in malignant cell transformation and cancer progression. HMGA1P6 and HMGAP17 act as microRNA decoy for HMGA1 and other cancer-related genes upregulating their protein levels. We have previously shown that they are upregulated in several human carcinomas, and their expression positively correlates with a poor prognosis and an advanced cancer stage. To evaluate in vivo oncogenic activity of HMGA1 pseudogenes, we have generated a HMGA1P7 transgenic mouse line overexpressing this pseudogene. By a mean age of 12 months, about 50% of the transgenic mice developed splenomegaly and accumulation of lymphoid cells in several body compartments. For these mice FACS and immunohistochemical analyses suggested the diagnosis of B-cell lymphoma that was further supported by clonality analyses and RNA expression profile of the pathological tissues of the HMGA1P7 transgenic tissues. Therefore, these results clearly demonstrate the oncogenic activity of HMGA1 pseudogenes in vivo.
Topics: Animals; Flow Cytometry; HMGA1a Protein; Immunohistochemistry; Lymphocytes; Lymphoma, B-Cell; Mice; Mice, Transgenic; NIH 3T3 Cells; Pseudogenes; RNA-Seq
PubMed: 32341372
DOI: 10.1038/s41598-020-62974-0 -
Science Advances Oct 2021Pseudogenes, noncoding homologs of protein-coding genes, once considered nonfunctional evolutionary relics, have recently been linked to patient prognoses and cancer...
Pseudogenes, noncoding homologs of protein-coding genes, once considered nonfunctional evolutionary relics, have recently been linked to patient prognoses and cancer subtypes. Despite this potential clinical importance, only a handful of >12,000 pseudogenes in humans have been characterized in cancers to date. Here, we describe a previously unrecognized role for pseudogenes as potent epigenetic regulators that can demethylate and activate oncogenes. We focused on , a known oncogene in hepatocellular carcinoma (HCC) with eight pseudogenes. Using a locus-specific demethylating technology, we identified the critical CpG region for SALL4 expression. We demonstrated that pseudogene 5 hypomethylates this region through interaction with DNMT1, resulting in SALL4 up-regulation. Intriguingly, pseudogene 5 is significantly up-regulated in a hepatitis B virus model before SALL4 induction, and both are increased in patients with HBV-HCC. Our results suggest that pseudogene-mediated demethylation represents a novel mechanism of oncogene activation in cancer.
PubMed: 34597139
DOI: 10.1126/sciadv.abg1695 -
Scientific Reports Mar 2021We identified and characterized the pseudogene complements of five plant species: four dicots (Arabidopsis thaliana, Vitis vinifera, Populus trichocarpa and Phaseolus...
We identified and characterized the pseudogene complements of five plant species: four dicots (Arabidopsis thaliana, Vitis vinifera, Populus trichocarpa and Phaseolus vulgaris) and one monocot (Oryza sativa). Retroposition was considered of modest importance for pseudogene formation in all investigated species except V. vinifera, which showed an unusually high number of retro-pseudogenes in non coding genic regions. By using a pipeline for the classification of sequence duplicates in plant genomes, we compared the relative importance of whole genome, tandem, proximal, transposed and dispersed duplication modes in the pseudo and functional gene complements. Pseudogenes showed higher tendencies than functional genes to genomic dispersion. Dispersed pseudogenes were prevalently fragmented and showed high sequence divergence at flanking regions. On the contrary, those deriving from whole genome duplication were proportionally less than expected based on observations on functional loci and showed higher levels of flanking sequence conservation than dispersed pseudogenes. Pseudogenes deriving from tandem and proximal duplications were in excess compared to functional loci, probably reflecting the high evolutionary rate associated with these duplication modes in plant genomes. These data are compatible with high rates of sequence turnover at neutral sites and double strand break repairs mediated duplication mechanisms.
Topics: Arabidopsis; Conserved Sequence; Evolution, Molecular; Gene Duplication; Gene Expression Regulation, Plant; Genes, Plant; Genetic Loci; Multigene Family; Oryza; Phaseolus; Populus; Pseudogenes; Vitis
PubMed: 33674668
DOI: 10.1038/s41598-021-84778-6 -
Scientific Reports May 2023Accumulating evidence shows that pseudogenes can function as microRNAs (miRNAs) sponges and regulate gene expression. Mining potential interactions between pseudogenes...
Accumulating evidence shows that pseudogenes can function as microRNAs (miRNAs) sponges and regulate gene expression. Mining potential interactions between pseudogenes and miRNAs will facilitate the clinical diagnosis and treatment of complex diseases. However, identifying their interactions through biological experiments is time-consuming and labor intensive. In this study, an ensemble learning framework with similarity kernel fusion is proposed to predict pseudogene-miRNA associations, named ELPMA. First, four pseudogene similarity profiles and five miRNA similarity profiles are measured based on the biological and topology properties. Subsequently, similarity kernel fusion method is used to integrate the similarity profiles. Then, the feature representation for pseudogenes and miRNAs is obtained by combining the pseudogene-pseudogene similarities, miRNA-miRNA similarities. Lastly, individual learners are performed on each training subset, and the soft voting is used to yield final decision based on the prediction results of individual learners. The k-fold cross validation is implemented to evaluate the prediction performance of ELPMA method. Besides, case studies are conducted on three investigated pseudogenes to validate the predict performance of ELPMA method for predicting pseudogene-miRNA interactions. Therefore, all experiment results show that ELPMA model is a feasible and effective tool to predict interactions between pseudogenes and miRNAs.
Topics: MicroRNAs; Pseudogenes; Machine Learning; Computational Biology; Algorithms
PubMed: 37258695
DOI: 10.1038/s41598-023-36054-y -
Genome Biology Nov 2022Pseudogenes are excellent markers for genome evolution, which are emerging as crucial regulators of development and disease, especially cancer. However, systematic...
BACKGROUND
Pseudogenes are excellent markers for genome evolution, which are emerging as crucial regulators of development and disease, especially cancer. However, systematic functional characterization and evolution of pseudogenes remain largely unexplored.
RESULTS
To systematically characterize pseudogenes, we date the origin of human and mouse pseudogenes across vertebrates and observe a burst of pseudogene gain in these two lineages. Based on a hybrid sequencing dataset combining full-length PacBio sequencing, sample-matched Illumina sequencing, and public time-course transcriptome data, we observe that abundant mammalian pseudogenes could be transcribed, which contribute to the establishment of organ identity. Our analyses reveal that developmentally dynamic pseudogenes are evolutionarily conserved and show an increasing weight during development. Besides, they are involved in complex transcriptional and post-transcriptional modulation, exhibiting the signatures of functional enrichment. Coding potential evaluation suggests that 19% of human pseudogenes could be translated, thus serving as a new way for protein innovation. Moreover, pseudogenes carry disease-associated SNPs and conduce to cancer transcriptome perturbation.
CONCLUSIONS
Our discovery reveals an unexpectedly high abundance of mammalian pseudogenes that can be transcribed and translated, and these pseudogenes represent a novel regulatory layer. Our study also prioritizes developmentally dynamic pseudogenes with signatures of functional enrichment and provides a hybrid sequencing dataset for further unraveling their biological mechanisms in organ development and carcinogenesis in the future.
Topics: Humans; Mice; Animals; Pseudogenes; Genome; Mammals; Sequence Analysis, DNA; Neoplasms
PubMed: 36348461
DOI: 10.1186/s13059-022-02802-y